The dual facets of MiRNA in modulating NF-κB in breast cancer

Breast cancer (BC) remains a leading cause of cancer-related mortality among women globally, especially among women aged 45-55 years. A key driver of tumor progression, metastasis, and therapy resistance in BC is the aberrant activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a proinflammatory transcription factor. Concurrently, microRNAs (miRNAs), a class of small non-coding RNAs, have emerged as critical post-transcriptional regulators of gene expression, influencing oncogenesis, immune response, apoptosis, and therapeutic outcomes.

Studies have revealed a complex interplay between miRNAs and NF-κB, wherein miRNAs exhibit context-dependent roles, functioning as either tumor suppressors or oncogenic regulators that modulate NF-κB signaling through direct or indirect mechanisms, modulating NF-κB signaling via direct or indirect mechanisms. This dual regulatory capacity presents unique therapeutic opportunities to either suppress oncogenic NF-κB signaling through tumor suppressor miRNAs (TS-miRs) or inhibit oncogenic miRNAs (OncomiRs) that potentiate NF-κB activity. This review presents a comprehensive overview of how miRNAs modulate NF-κB pathways in BC, outlines recent preclinical advances in miRNA delivery technologies, and discusses the clinical implications of miRNA-based therapeutics.

We emphasize the translational potential of miRNAs as emerging therapeutic modalities and predictive biomarkers for the personalized management of BC.